Disordered intestinal flora and discordant immune response are associated with the development of ulcerative colitis (UC). Recent work has described the ability of macrophages to undergo repolarization toward a proinflammatory M1 or anti-inflammatory M2 phenotype in response to particular bacterium-derived signals. Fusobacterium nucleatum ( F. nucleatum, Fn ) is a species of intestinal commensal bacteria with potential pathogenicity, but its association with UC and how it may contribute to progression of UC is largely unknown. In this study, we provide new evidence that F. nucleatum accumulated heavily in the intestine of UC patients and was accompanied by the secretion of IFN-γ and the skewing of M1 macrophages. Mechanistically, our data showed that F. nucleatum aggravated dextran sodium sulfate (DSS)-induced colitis in the production of Th1-related cytokines IFN-γ through the AKT2 signaling pathway in vitro and in vivo . To further confirm the disease-relevance of these shifts in macrophage repolarization in response to F. nucleatum , stimulated bone marrow-derived macrophages (BMDMs) were transferred into recipient mice with DSS colitis. This transfer resulted in increased disease activity and inflammatory cytokine production. Taken together, we show clearly that F. nucleatum can promote the progression of UC via proinflammatory M1 macrophage skewing, and targeting F. nucleatum or AKT2 signaling may be a viable means of blocking development of UC.
Background This study aimed to investigate whether an increased proton pump inhibitor (PPI) dose enhanced the efficacy of Helicobacter pylori (H. pylori) eradication and determine the appropriate cutoff intragastric pH value that could predict H. pylori eradication with bismuth‐based quadruple therapy. Materials and Methods A total of 207 H. pylori infected, treatment naive patients were enrolled in this prospective, open‐label, randomized controlled trial. Patients were randomly allocated into Eso40‐group (esomeprazole 40 mg bid) and Eso20‐group (esomeprazole 20 mg bid), and their CYP2C19 genotyping status was assessed. The 24‐h intragastric pH monitoring on day 7 was performed, and percentage of time gastric pH ≥ 3, ≥4, ≥5, and ≥6 (pH holding time ratios; HTRs) were measured. H. pylori eradication was evaluated using 13C‐urea breath test. Results No significant difference in the eradication rates was observed between two groups. The median 24‐h intragastric pH value was not significant different between two groups but the Eso40 Group had a significant higher pH4 HTRs (91.11% [95%CI: 87.50%–95.83%] vs. 95.83% [95.83%–100%]; p = .002). Additionally, the median 24‐h intragastric pH value showed significantly difference between two groups in EM genotype (Eso20 Group 6.00 [95%CI; 5.75–6.15] vs. Eso40 Group 6.30 [6.05–6.30]; p = .019). Similar results were observed in pH4 HTRs. There were significant differences in intragastric pH value (6.10 [95%CI: 4.40–7.00] vs. 5.65 [4.85–5.95], p = .038) and in pH4 HTRs (96% [95%CI: 92.00%–96.00%] vs. 87.5% [67.00%–100.0%], p = .019) between eradication‐successful and eradication‐failed patients. Statistical analysis suggested that the median intragastric pH = 5.7 could identify the success of H. pylori eradication. Conclusions Bismuth‐based quadruple therapy resulted in high H. pylori eradication rates either in PPI standard or double doses. Double dose of esomeprazole is associated with better intragastric acid suppression. A median 24‐h intragastric pH of 5.7 could be appropriate cutoff value for predicting the successful H. pylori eradication.
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